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NUCLEIC ACID

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Nucleic acid

  • Friedrich Miescher in 1869 isolated what he called nuclein from the nuclei of pus cells

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  • Nuclein was shown to have acidic properties, hence it became called nucleic acid

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  • The nucleic acids play a central role in the storage and expression of genetic information

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  • Nucleic acids are unbranched polymers of nucleotides

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History:

  • 1869: isolated DNA from salmon sperm (Friedrich Miescher)
  • 1944: proved DNA is genetic materials (Avery et al.)
  • 1953: discovered DNA double helix (Watson and Crick)
  • 1968: decoded the genetic codes (Nirenberg)
  • 1981: invented DNA sequencing method (Gilbert and Sanger)
  • 1987: launched the human genome project
  • 2001: accomplished the draft map of human genome

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Functions:

Nucleic Acid Functions:

  • Storage of genetic info (DNA)

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  • Transmission of genetic info (mRNA)

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  • Processing of genetic information

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  • Protein synthesis (tRNA and rRNA)

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Introduction:

  • DNA and RNA molecules are linear polymer built from individual units called nucleotide connected by bonds called phosphodiester linkages

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  • DNA and RNA are used to store and pass genetic information from one generation to the next

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Conti……

  • Nucleic acid is a very large molecule made up of a long chain of sub-units

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  • The sub-units are called nucleotides

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  • Each nucleotide is made up of

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    • A sugar called deoxyribose

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    • A phosphate group -PO4

    • A nitrogenous base

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Conti….

  • In both DNA and RNA molecules each nucleotide consist of a linear backbone that consists of repeating sugar-phosphate units

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  • However it is the nitrogenous bases that are responsible for storing the genetic information

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Composition of Nucleic acid:

  • Sugar Component:
  • Although both DNA and RNA molecules contain sugar

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  • DNA contain a deoxyribose sugar that lacks a hydroxyl group on the second carbon

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  • The absence of this –OH group stabilizes the structure of DNA by making it more resistant to hydrolysis

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Conti…

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Backbone and phosphodiester linkage:

  • The sugar of nucleic acid are connected to one another by 3՜- to 5՜- via a phosphodiester linkage

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  • The –OH group on the 3rd carbon of one sugar is connected to the –OH group on the 5th carbon of an adjacent sugar via a phosphate group

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  • This chain of repeating sugar-phosphate units make up the backbone of the nucleic acid

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  • The backbone remain constant and unchanged

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Conti…

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Conti…

  • Phosphate group contain a negative charge. This means that:

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    • In an aqueous environment these hydrophilic regions interact with the polar molecules to stabilizes the structure of DNA

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    • The Phosphodiester linkages are much less likely to be attacked by nucleophilic agents, which means that they are less susceptible to hydrolysis

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Nitrogenous bases:

  • Although the backbone does not change, the bases vary from one nucleotide to the next
  • There are two categories of bases:
    • Purines
    • Pyrimidines
  • Purines consist of two fused ring structures
  • Both DNA and RNA have two types of Purines
    • Adenine
    • Guanine

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Conti…

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  • Pyrimidines consist of a single ring. DNA contain two Pyrimidines
    • Thymine
    • Cytosine
  • In RNA the thymine is replaced by uracil

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Conti…

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Conti…

  • The sequence of these bases is unique to the nucleic acid

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  • Because it is the base that vary from nucleotide along the liner polymer

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  • It’s the sequences of bases that determine the genetic code

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Nucleoside:

  • A unit consisting of a sugar molecule attached covalently to a nitrogenous base is called a nucleoside
  • Nucleosides are named by changing the nitrogen base ending to -osine for purines and –idine for pyrimidines
  • The nucleoside in RNA are:
    • Adenosine
    • Guanosine
    • Cytidine
    • Uridine

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Conti…

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Conti…

  • Nucleoside in the DNA are:
    • Deoxyadenosine

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    • Deoxyguanosine

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    • Deoxycytidine

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    • Deoxythymidine

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Conti…

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Nucleotide:

  • Nucleotide consist of

    • Nitrogenous base

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    • Pentose

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    • Phosphate

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Conti…

  • The nucleotide in the RNA are:

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    • Adenylate
    • Guanylate
    • Cytidylate
    • Uridylate

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  • A nucleotide is a nucleoside that forms a phosphate ester with the C5’ OH group of ribose or deoxyribose

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Conti…

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Conti…

  • The nucleotide in the DNA are called:
    • Deoxy Adenylate

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    • Deoxy Guanylate

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    • Deoxy Cytidylate

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    • Deoxy thymidylate

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Conti…

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Conti….

  • Number of phosphate groups determines nomenclature
  • Monophosphate e.g. AMP

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  • Diphosphate e.g. ADP

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  • Triphosphate e.g. ATP

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β-N-Glycosidic Bond:

  • In nucleotides the pentose ring is attached to the nucleobase via N-glycosidic bond
  • The bond is formed to the anomeric carbon of the sugar in β-configuration
  • The bond is formed:
    • to position N1 in pyrimidines
    • to position N9 in purines
  • This bond is quite stable toward hydrolysis, especially in pyrimidines
  • Bond cleavage is catalyzed by acid

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AMP, ADP and ATP:

  • Additional phosphate groups can be added to the nucleoside 5’-monophosphates to form diphosphates and triphosphates
  • ATP is the major energy source for cellular activity

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